The levels of local angiotensin II (AngII) and activation of p38 mitogen-activated protein kinase and NF-kB signaling pathways in splenic vein vasculopathy of portal hypertension

Objective To investigate the levels of local angiotensin II (AngII) and activation of p38MAPK and NF-kB signaling pathways in human splenic vein vasculopathy of portal hypertension (PHT) and discuss the possible action mechanism.Methods Twenty-six patients with posthepatitic cirrhosis PHT admitted to the first affiliated Hospital of Fujian Medical University served as PHT group,and 10 patients with traumatic spleen rupture during the same period as the control group.RIA method was used to determine local AngII level in splenic veins.The expression of NF-κB and Phospho-p38 in humansplenic veins was assayed by immunohistochemistry and Western blot.Vascular smooth muscle cells (VSMCs) were obtained from human splenic vein of PHT.The expression of NF-κB and Phospho-p38 in human splenic veins and VSMC of splenic veins was detected by Western blot.Results The levels of local AngII in the splenic veins of PHT group were (248.91±48.31) ng/L,significantly higher than those in the control group [(143.35±36.45) ng/L] (P<0.01).The expression of NF-κB and Phospho-p38 in the splenic vein of PHT group was stronger than in control group (P<0.01).Within a certain concentration coverage,AngII (1×10-8-1×10-6 mol/L) increased the expression of NF-κB and Phospho-p38 in VSMC of splenic veins in a dose-dependent manner.Conclusion During PHT,in splenic vein the level of AngII was enhanced and the expression of NF-kB and phospho-p38 increased.AngII could activate the NF-κB and p38MAPK signaling pathways in the VSMCs of splenic vein.AngII may be critical for the formation and maintenance of PHT. Key words: Portal Hypertension; Splenic vein; Angiotensin Ⅱ; NF-kappa B; p38MAPK